Madras Motor Neuron Disease

Motor neurons are a type of cells in the nervous system that conveys impulses which directly or indirectly control muscle movements. Madras Motor Neuron Disease (MMND), also referred to as Madras pattern motor neuron disease, is a rare young age onset progressive neuromuscular disease taking relatively benign course. MMND has predominant geographic distribution in southern India.

Originally identified in 1970 in the southern city of Madras, India, there are 152 MMND cases have been reported from India until 2009. Outside this core region, as of 2009, solitary cases of each in China, Italy, Korea, Thailand and Turkey have also been reported, totaling 157 cases throughout the world. MMND is equally represented in both sexes. Nearly all of them are from four southern Indian states of Andhra Pradesh, Karnataka, Kerala and Tamil Nadu

Molecular pathogenesis of the condition is the unanswered important question in MMND and no published scientific report is available in this respect. Multipronged approach is required to evaluate various causal factors such as the genetic, environmental and perhaps ethnic factor as well, considering its geographic preponderance.

Majority of the patients look slender. The hallmark of MMND is sensorineural deafness (hearing loss due to nerve defect), atrophy and weakness of the limb muscles, cranial nerve palsies involving cranial nerves VII, IX and XII, facial and bulbar muscles (kind of muscles that control the chewing, swallowing and speech) with disease onset at young age (generally before the age of 15). In addition to above symptoms a variant of MMND (MMNDV) is presented with bilateral optic atrophy (loss of optic nerve fibers on both sides) or visual impairment. Though majority of the MMND cases appear to be sporadic, a few familial cases (FMMND) have been identified as well. While recognizing the paucity in familial cases, the mode of inheritance within FMMND is suggested to be predominantly autosomal recessive.

Table 1. Select clinical characteristics from a large group of MMND patients. Excerpted from a detailed scientific study in J Neurol Sci. 2008;269:65-73.

Biochemical study: Low plasma citrate and elevated pyruvate levels and resulting low citrate/pyruvate ratio have been observed in a group of four MMND patients compared to normal subjects. But this observation is yet to be reproduced and is currently not considered to be of diagnostic significance.

Pathological study: Observations on postmortem spinal cord reveal an extreme loss of anterior horn cells, demyelination and sclerosis of the ventrolateral columns. Bulbar motor nuclei and cochlear nucleus show neuronal depletion. Inflammatory etiology in MMND is suggested.

MMND, a subgroup of broader group called MND (motor neuron disease), closely resembles several other disease conditions, including relatively common ALS (amyotrohic lateral sclerosis) and are considered in the differential diagnosis. There are arguments if MMND and Brown-Vialetto-Van Laere syndrome (BVVL) described from Western Europe are similar clinical entities. However, there are several finer clinical features that differentiate MMND from BVVL.

Figure 1. A schematic of closely related diseases within MND. Grey shades relate clinical proximity among the diseqases. This chart is based on differential diagnostic algorithm described for BVVL syndrome in Orphanet J Rare Dis. 2008;3:9.

There is no specific treatment for MMND is available yet. Intravenous immunoglobulin administered in one case showed moderate improvement in certain symptoms. Yet, immunoglobulin treatment is based on the assumption of inflammatory etiology of MMND, but not a proven treatment. Rarity of MNND in itself is an impediment for evolving a possible treatment. Symptomatic treatment and supportive care, such as offering hearing aids, are part of MMND management that might help maintain patients' routine activities. The positive aspect of this disease is that many patients continue to live for several decades after the onset of the disease.

References and further readings

Meenakshisundaram E, Jagannathan K, Ramamurthi B. Clinical pattern of motor neuron disease seen in younger age groups in Madras. Neurol India. 1970;18(Suppl.1):109-112.

Valmikinathan K, Mascreen M, Meenakshisundaram E, Snehalatha C. Biochemical aspects of motor neurone disease--Madras pattern. J Neurol Neurosurg Psychiatry. 1973;36:753-756.

Shankar SK, Gourie-Devi M, Shankar L, Yasha TC, Santosh V, Das S. Pathology of Madras type of motor neuron disease (MMND)--a histological and immunohistochemical study.Acta Neuropathol. 2000;99:428-434.

Nalini A, Yamini BK, Gayatri N, Thennarasu K, Gope R. Familial Madras motor neuron disease (FMMND): study of 15 families from southern India. J Neurol Sci. 2006;250:140-146.

Nalini A, Thennarasu K, Yamini BK, Shivashankar D, Krishna N. Madras motor neuron disease (MMND): clinical description and survival pattern of 116 patients from Southern India seen over 36 years (1971-2007). J Neurol Sci. 2008;269:65-73.

Sathasivam S. Brown-Vialetto-Van Laere syndrome. Orphanet J Rare Dis. 2008;3:9.

Contributor: Duraiswamy Navaneetham PhD.

Temple University School of Medicine

Philadelphia, PA, USA

February 2010